BRPI0610934A2 - inibidores de adenilato ciclase solúvel - Google Patents

inibidores de adenilato ciclase solúvel Download PDF

Info

Publication number: BRPI0610934A2
Authority: BR; Brazil
Prior art keywords: alkyl; acyl; aryl; identically; differently
Prior art date: 2005-06-08

Application number

BRPI0610934-9A

Other languages

English (en)

Portuguese (pt)

Inventor

Bernd Buchmann

Nguyen Duy

Martin Fritsch

Bernd Menzebach

Ulf Boemer

Original Assignee

Bayer Schering Pharma Ag

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2005-06-08

Filing date

2006-06-07

Publication date

2010-08-03

2006-06-07 Application filed by Bayer Schering Pharma Ag filed Critical Bayer Schering Pharma Ag

2010-08-03 Publication of BRPI0610934A2 publication Critical patent/BRPI0610934A2/pt

Links

108060000200 adenylate cyclase Proteins 0.000 title description 18
102000030621 adenylate cyclase Human genes 0.000 title description 18
239000003112 inhibitor Substances 0.000 title description 9
150000001875 compounds Chemical class 0.000 claims abstract description 54
229940126601 medicinal product Drugs 0.000 claims abstract description 13
238000004519 manufacturing process Methods 0.000 claims abstract description 11
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 58
125000002252 acyl group Chemical group 0.000 claims description 48
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 46
-1 C1-C6-aryl Chemical group 0.000 claims description 45
229910052736 halogen Inorganic materials 0.000 claims description 44
150000002367 halogens Chemical class 0.000 claims description 44
125000000217 alkyl group Chemical group 0.000 claims description 38
125000004093 cyano group Chemical group *C#N 0.000 claims description 37
229910052739 hydrogen Inorganic materials 0.000 claims description 34
239000001257 hydrogen Substances 0.000 claims description 34
125000003545 alkoxy group Chemical group 0.000 claims description 33
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 32
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 24
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 23
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 23
229910052757 nitrogen Inorganic materials 0.000 claims description 23
229910052760 oxygen Inorganic materials 0.000 claims description 23
239000001301 oxygen Substances 0.000 claims description 23
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 22
239000011593 sulfur Substances 0.000 claims description 22
229910052717 sulfur Inorganic materials 0.000 claims description 22
150000003839 salts Chemical class 0.000 claims description 20
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 19
125000003118 aryl group Chemical group 0.000 claims description 18
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 13
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 12
125000001072 heteroaryl group Chemical group 0.000 claims description 11
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 10
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
229910052731 fluorine Inorganic materials 0.000 claims description 8
239000011737 fluorine Substances 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
201000010099 disease Diseases 0.000 claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
125000005843 halogen group Chemical group 0.000 claims description 7
125000005842 heteroatom Chemical group 0.000 claims description 7
229940124530 sulfonamide Drugs 0.000 claims description 7
150000003456 sulfonamides Chemical class 0.000 claims description 7
OGCTVAZRMAGZCR-UHFFFAOYSA-N 5-[(4-tert-butylphenyl)sulfonylamino]-3-phenyl-1-benzothiophene-2-carboxylic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1S(=O)(=O)NC1=CC=C(SC(C(O)=O)=C2C=3C=CC=CC=3)C2=C1 OGCTVAZRMAGZCR-UHFFFAOYSA-N 0.000 claims description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
239000000460 chlorine Substances 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
125000006823 (C1-C6) acyl group Chemical group 0.000 claims description 5
101710095468 Cyclase Proteins 0.000 claims description 5
239000002253 acid Substances 0.000 claims description 5
150000001408 amides Chemical class 0.000 claims description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 5
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
239000000825 pharmaceutical preparation Substances 0.000 claims description 4
229920006395 saturated elastomer Polymers 0.000 claims description 4
239000003433 contraceptive agent Substances 0.000 claims description 3
230000002401 inhibitory effect Effects 0.000 claims description 3
BKMMTJMQCTUHRP-UHFFFAOYSA-N 2-aminopropan-1-ol Chemical compound CC(N)CO BKMMTJMQCTUHRP-UHFFFAOYSA-N 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims description 2
230000002254 contraceptive effect Effects 0.000 claims description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 2
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
XEYPANZFAQJADI-UHFFFAOYSA-N 3-phenyl-1-benzothiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC2=CC=CC=C2C=1C1=CC=CC=C1 XEYPANZFAQJADI-UHFFFAOYSA-N 0.000 claims 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims 1
230000004060 metabolic process Effects 0.000 claims 1
125000000565 sulfonamide group Chemical group 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
239000000243 solution Substances 0.000 description 24
239000000126 substance Substances 0.000 description 22
238000012360 testing method Methods 0.000 description 19
238000006243 chemical reaction Methods 0.000 description 16
IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 15
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
230000000694 effects Effects 0.000 description 13
230000008010 sperm capacitation Effects 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
238000000034 method Methods 0.000 description 11
102000004190 Enzymes Human genes 0.000 description 10
108090000790 Enzymes Proteins 0.000 description 10
230000030120 acrosome reaction Effects 0.000 description 10
230000035558 fertility Effects 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
QTANTQQOYSUMLC-UHFFFAOYSA-O Ethidium cation Chemical compound C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 QTANTQQOYSUMLC-UHFFFAOYSA-O 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
238000011097 chromatography purification Methods 0.000 description 8
150000002431 hydrogen Chemical group 0.000 description 8
ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 7
ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 7
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 7
239000013078 crystal Substances 0.000 description 7
238000011156 evaluation Methods 0.000 description 7
239000002904 solvent Substances 0.000 description 7
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
230000009467 reduction Effects 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
210000001550 testis Anatomy 0.000 description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 5
238000004364 calculation method Methods 0.000 description 5
230000008878 coupling Effects 0.000 description 5
238000010168 coupling process Methods 0.000 description 5
238000005859 coupling reaction Methods 0.000 description 5
238000001514 detection method Methods 0.000 description 5
238000002866 fluorescence resonance energy transfer Methods 0.000 description 5
230000006870 function Effects 0.000 description 5
239000012528 membrane Substances 0.000 description 5
239000008188 pellet Substances 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
125000005605 benzo group Chemical group 0.000 description 4
YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 4
230000004663 cell proliferation Effects 0.000 description 4
238000011534 incubation Methods 0.000 description 4
208000000509 infertility Diseases 0.000 description 4
230000036512 infertility Effects 0.000 description 4
239000000203 mixture Substances 0.000 description 4
108090000623 proteins and genes Proteins 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
238000010186 staining Methods 0.000 description 4
239000000725 suspension Substances 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
101000775498 Homo sapiens Adenylate cyclase type 10 Proteins 0.000 description 3
102000001708 Protein Isoforms Human genes 0.000 description 3
108010029485 Protein Isoforms Proteins 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
230000027455 binding Effects 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
125000004122 cyclic group Chemical group 0.000 description 3
238000010790 dilution Methods 0.000 description 3
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229940011871 estrogen Drugs 0.000 description 3
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MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 3
125000001153 fluoro group Chemical group F* 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
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108020004999 messenger RNA Proteins 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
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229940127198 soluble adenylyl cyclase inhibitor Drugs 0.000 description 3
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CYIIBZKKCJFITL-UHFFFAOYSA-N 5-[(4-tert-butylphenyl)sulfonylamino]-n-(2-morpholin-4-ylethyl)-3-phenyl-1-benzothiophene-2-carboxamide Chemical compound C1=CC(C(C)(C)C)=CC=C1S(=O)(=O)NC1=CC=C(SC(C(=O)NCCN2CCOCC2)=C2C=3C=CC=CC=3)C2=C1 CYIIBZKKCJFITL-UHFFFAOYSA-N 0.000 description 2
XEOYNMJRDLWBIU-UHFFFAOYSA-N 5-[(4-tert-butylphenyl)sulfonylamino]-n-(oxan-4-yl)-3-phenyl-1-benzothiophene-2-carboxamide Chemical compound C1=CC(C(C)(C)C)=CC=C1S(=O)(=O)NC1=CC=C(SC(C(=O)NC2CCOCC2)=C2C=3C=CC=CC=3)C2=C1 XEOYNMJRDLWBIU-UHFFFAOYSA-N 0.000 description 2
229920000858 Cyclodextrin Polymers 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
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PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 2
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JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
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SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
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AAIJKLTYGAVEMX-UHFFFAOYSA-N ethyl 3-bromo-5-[(4-tert-butylphenyl)sulfonylamino]-1-benzothiophene-2-carboxylate Chemical compound C1=C2C(Br)=C(C(=O)OCC)SC2=CC=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 AAIJKLTYGAVEMX-UHFFFAOYSA-N 0.000 description 2
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229910052748 manganese Inorganic materials 0.000 description 2
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HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
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125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
238000011813 knockout mouse model Methods 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
230000004576 lipid-binding Effects 0.000 description 1
239000002502 liposome Substances 0.000 description 1
230000002101 lytic effect Effects 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
QWDJLDTYWNBUKE-UHFFFAOYSA-L magnesium bicarbonate Chemical compound [Mg+2].OC([O-])=O.OC([O-])=O QWDJLDTYWNBUKE-UHFFFAOYSA-L 0.000 description 1
229910000022 magnesium bicarbonate Inorganic materials 0.000 description 1
235000014824 magnesium bicarbonate Nutrition 0.000 description 1
239000002370 magnesium bicarbonate Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000011565 manganese chloride Substances 0.000 description 1
235000002867 manganese chloride Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
208000030159 metabolic disease Diseases 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
PHISOQDTXLYKKV-UHFFFAOYSA-N n-(2-acetamidoethyl)-5-[(4-tert-butylphenyl)sulfonylamino]-3-phenyl-1-benzothiophene-2-carboxamide Chemical compound C1=C2C(C=3C=CC=CC=3)=C(C(=O)NCCNC(=O)C)SC2=CC=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 PHISOQDTXLYKKV-UHFFFAOYSA-N 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
231100000957 no side effect Toxicity 0.000 description 1
108020004707 nucleic acids Proteins 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000003585 oxepinyl group Chemical group 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000005019 pattern of movement Effects 0.000 description 1
230000035515 penetration Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
229960003531 phenolsulfonphthalein Drugs 0.000 description 1
125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
229920001515 polyalkylene glycol Polymers 0.000 description 1
108091033319 polynucleotide Proteins 0.000 description 1
102000040430 polynucleotide Human genes 0.000 description 1
239000002157 polynucleotide Substances 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
238000000079 presaturation Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
238000011002 quantification Methods 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
239000002994 raw material Substances 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
229940043230 sarcosine Drugs 0.000 description 1
238000004062 sedimentation Methods 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000007787 solid Substances 0.000 description 1
210000001082 somatic cell Anatomy 0.000 description 1
230000000392 somatic effect Effects 0.000 description 1
230000019100 sperm motility Effects 0.000 description 1
230000021595 spermatogenesis Effects 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
210000000130 stem cell Anatomy 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
230000002381 testicular Effects 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
238000010792 warming Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D333/70—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Reproductive Health (AREA)
Endocrinology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Furan Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Saccharide Compounds (AREA)

BRPI0610934-9A 2005-06-08 2006-06-07 inibidores de adenilato ciclase solúvel BRPI0610934A2 (pt)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DE102005027274A DE102005027274A1 (de)	2005-06-08	2005-06-08	Inhibitoren der löslichen Adenylatzyklase
DE102005027274.6		2005-06-08
PCT/EP2006/005608 WO2006131398A2 (en)	2005-06-08	2006-06-07	Inhibitors of soluble adenylate cyclase

Publications (1)

Publication Number	Publication Date
BRPI0610934A2 true BRPI0610934A2 (pt)	2010-08-03

Family

ID=37398540

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BRPI0610934-9A BRPI0610934A2 (pt)	2005-06-08	2006-06-07	inibidores de adenilato ciclase solúvel

Country Status (23)

Country	Link
EP (1)	EP1888058B1 (de)
JP (1)	JP2008542422A (de)
KR (1)	KR20080016617A (de)
CN (1)	CN101193631A (de)
AR (1)	AR054378A1 (de)
AT (1)	ATE431736T1 (de)
AU (1)	AU2006256857A1 (de)
BR (1)	BRPI0610934A2 (de)
CA (1)	CA2606692A1 (de)
CR (1)	CR9578A (de)
DE (2)	DE102005027274A1 (de)
DO (1)	DOP2006000130A (de)
EA (1)	EA200702590A1 (de)
EC (1)	ECSP078024A (de)
GT (1)	GT200600244A (de)
IL (1)	IL186914A0 (de)
MX (1)	MX2007015493A (de)
NO (1)	NO20080104L (de)
PE (1)	PE20061488A1 (de)
TW (1)	TW200716090A (de)
UY (1)	UY29583A1 (de)
WO (1)	WO2006131398A2 (de)
ZA (1)	ZA200800153B (de)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE102006014319B4 (de) *	2006-03-23	2009-01-08	Bayer Schering Pharma Aktiengesellschaft	Inhibitoren der löslichen Adenylatzyklase
EP2036906A1 (de) *	2007-09-05	2009-03-18	Bayer Schering Pharma Aktiengesellschaft	Azaindole als Inhibitoren der löslichen Adenylatzyklase
AU2022403203B2 (en)	2021-12-01	2025-09-25	Pfizer Inc.	3-phenyl-1-benzothiophene-2-carboxylic acid derivatives as branched-chain alpha keto acid dehydrogenase kinase inhibitors for the treatment of diabetes, kidney diseases, nash and heart failure

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2635776B1 (fr) *	1988-09-01	1993-06-11	Rhone Poulenc Agrochimie	Derives amides, procede pour leur fabrication et compositions fongicides les contenant
WO2002020745A1 (en) *	2000-09-05	2002-03-14	University Of Virginia Patent Foundation	Human soluble testicular adenylyl cyclase
CN1880304B (zh) *	2001-06-28	2010-11-24	辉瑞产品公司	三酰胺取代的吲哚、苯并呋喃及苯并噻吩
WO2003024448A2 (en) *	2001-09-14	2003-03-27	Methylgene, Inc.	Inhibitors of histone deacetylase
UA79504C2 (en) *	2002-11-07	2007-06-25	Organon Nv	Indols for treating diseases associated with androgen receptors
EP1663242B1 (de) *	2003-08-07	2011-04-27	Rigel Pharmaceuticals, Inc.	2,4-pyrimidindiamin-verbindungen und verwendungen als antiproliferative mittel
US7935724B2 (en) *	2003-10-09	2011-05-03	Merck Hdac Research, Llc	Thiophene and benzothiophene hydroxamic acid derivatives
EP1706114B1 (de) *	2004-01-21	2012-12-26	Cornell Research Foundation, Inc.	Chemische inhibitoren löslicher adenylylcyclase (sac)
EP1735319B1 (de) *	2004-03-26	2017-05-03	MethylGene Inc.	Histondeacetylase-hemmer
DE102004047272A1 (de) *	2004-09-24	2006-04-06	Schering Ag	Inhibitoren der löslichen Adenylatzyklase

2005
- 2005-06-08 DE DE102005027274A patent/DE102005027274A1/de not_active Withdrawn
2006
- 2006-06-07 WO PCT/EP2006/005608 patent/WO2006131398A2/en not_active Ceased
- 2006-06-07 EP EP06762012A patent/EP1888058B1/de not_active Not-in-force
- 2006-06-07 JP JP2008515154A patent/JP2008542422A/ja active Pending
- 2006-06-07 KR KR1020077028637A patent/KR20080016617A/ko not_active Withdrawn
- 2006-06-07 AT AT06762012T patent/ATE431736T1/de not_active IP Right Cessation
- 2006-06-07 AR ARP060102365A patent/AR054378A1/es unknown
- 2006-06-07 GT GT200600244A patent/GT200600244A/es unknown
- 2006-06-07 PE PE2006000622A patent/PE20061488A1/es not_active Application Discontinuation
- 2006-06-07 UY UY29583A patent/UY29583A1/es not_active Application Discontinuation
- 2006-06-07 CA CA002606692A patent/CA2606692A1/en not_active Abandoned
- 2006-06-07 BR BRPI0610934-9A patent/BRPI0610934A2/pt not_active IP Right Cessation
- 2006-06-07 CN CNA2006800201485A patent/CN101193631A/zh active Pending
- 2006-06-07 EA EA200702590A patent/EA200702590A1/ru unknown
- 2006-06-07 MX MX2007015493A patent/MX2007015493A/es not_active Application Discontinuation
- 2006-06-07 AU AU2006256857A patent/AU2006256857A1/en not_active Abandoned
- 2006-06-07 DE DE602006006908T patent/DE602006006908D1/de not_active Expired - Fee Related
- 2006-06-08 TW TW095120397A patent/TW200716090A/zh unknown
- 2006-06-08 DO DO2006000130A patent/DOP2006000130A/es unknown
2007
- 2007-10-25 IL IL186914A patent/IL186914A0/en unknown
- 2007-12-07 CR CR9578A patent/CR9578A/es not_active Application Discontinuation
- 2007-12-17 EC EC2007008024A patent/ECSP078024A/es unknown
2008
- 2008-01-07 ZA ZA200800153A patent/ZA200800153B/xx unknown
- 2008-01-07 NO NO20080104A patent/NO20080104L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
DE602006006908D1 (de)	2009-07-02
DOP2006000130A (es)	2006-11-30
EP1888058B1 (de)	2009-05-20
DE102005027274A1 (de)	2006-12-14
CR9578A (es)	2008-03-06
KR20080016617A (ko)	2008-02-21
ATE431736T1 (de)	2009-06-15
AU2006256857A1 (en)	2006-12-14
ZA200800153B (en)	2009-03-25
NO20080104L (no)	2008-03-03
EP1888058A2 (de)	2008-02-20
CN101193631A (zh)	2008-06-04
JP2008542422A (ja)	2008-11-27
IL186914A0 (en)	2008-02-09
EA200702590A1 (ru)	2008-06-30
AR054378A1 (es)	2007-06-20
UY29583A1 (es)	2007-01-31
TW200716090A (en)	2007-05-01
GT200600244A (es)	2007-01-23
WO2006131398A2 (en)	2006-12-14
PE20061488A1 (es)	2007-02-03
MX2007015493A (es)	2008-02-22
ECSP078024A (es)	2008-01-23
WO2006131398A3 (en)	2007-04-19
CA2606692A1 (en)	2006-12-14

Legal Events

Date	Code	Title	Description
2012-06-05	B08F	Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette]	Free format text: REFERENTE AS 5A E 6A ANUIDADES.
2013-02-26	B08K	Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette]	Free format text: REFERENTE AO DESPACHO 8.6 PUBLICADO NA RPI 2161 DE 05/06/2012.

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RS56111B1 (sr)	2017-10-31	Ligandi opioidnih receptora i postupci njihove upotrebe i pripreme
DE102004047272A1 (de)	2006-04-06	Inhibitoren der löslichen Adenylatzyklase
EP1888058B1 (de)	2009-05-20	Inhibitoren der löslichen Adenylatzyklase
US7417066B2 (en)	2008-08-26	Inhibitors of soluble adenylate cyclase
CN101448788A (zh)	2009-06-03	作为可溶性腺苷酸环化酶的抑制剂的吲哚衍生物
US20090098189A1 (en)	2009-04-16	Azaindoles as inhibitors of soluble adenylate cyclase
KR20090008261A (ko)	2009-01-21	가용성 아데닐레이트 시클라제 억제제
KR20090007351A (ko)	2009-01-16	가용성 아데닐레이트 시클라제 억제제
US20070225284A1 (en)	2007-09-27	Inhibitors of soluble adenylate cyclase
HK1118485A (en)	2009-02-13	Inhibitors of soluble adenylate cyclase